What effects does lupus have on the kidneys and liver?

Effects of Lupus on the Kidneys and Liver

Lupus primarily affects the kidneys through lupus nephritis, which occurs in approximately 40% of patients with systemic lupus erythematosus (SLE) and can lead to chronic kidney disease and end-stage kidney disease in about 10% of patients after 10 years if not properly managed. 1

Kidney Involvement in Lupus

Lupus Nephritis

• Pathophysiology:

  • Immune complex deposition in the glomeruli
  • Complement activation
  • Inflammatory cell recruitment
  • Glomerular and tubulointerstitial inflammation 2
  • Development of tubulointerstitial inflammation, which is a better predictor of progression to renal failure than glomerular changes 3

• Clinical Manifestations:

  • Proteinuria (>500 mg/day warrants further investigation) 2
  • Hematuria
  • Elevated serum creatinine
  • Decreased glomerular filtration rate (eGFR)
  • Hypertension 2

• Monitoring Parameters:

  • Serum creatinine and eGFR
  • Urine protein:creatinine ratio
  • Urinary sediment analysis
  • Serum albumin
  • Blood pressure
  • Complement levels (C3, C4)
  • Anti-dsDNA antibody levels 2

• Complications:

  • Chronic kidney disease (CKD)
  • End-stage renal disease (ESRD) requiring dialysis or transplantation
  • Increased cardiovascular risk
  • Secondary immunodeficiency 4
  • Thrombotic microangiopathy, especially in patients with antiphospholipid antibodies 2

Risk Factors for Kidney Disease Progression

• Each flare of lupus nephritis increases risk of CKD progression
• Non-immune factors:
  • Obesity
  • Hypertension
  • High sodium or protein diets
  • Type 2 diabetes
  • Smoking
  • Nephrotoxic medications 4

Liver Involvement in Lupus

While the guidelines focus more extensively on kidney involvement, liver abnormalities can occur in lupus patients through several mechanisms:

Types of Liver Involvement

• Drug-induced liver injury:

  • From medications used to treat lupus (e.g., immunosuppressants)
  • Hydroxychloroquine, while generally beneficial for lupus, requires dose adjustment in patients with liver disease 2

• Lupus hepatitis:

  • Direct immune-mediated liver inflammation
  • Can present with elevated liver enzymes

• Associated autoimmune liver diseases:

  • Autoimmune hepatitis
  • Primary biliary cholangitis

• Vascular complications:

  • Budd-Chiari syndrome (in patients with antiphospholipid antibodies)
  • Hepatic vascular thrombosis

Management Considerations

Kidney Management

1. Regular monitoring:

   • Visits every 2-4 weeks for first 2-4 months after diagnosis or flare
   • Then according to response to treatment
   • Lifelong monitoring at least every 3-6 months 2

2. Pharmacological treatment:

   • Hydroxychloroquine is recommended for all SLE patients including those with lupus nephritis to:

     • Reduce renal flares
     • Limit renal and cardiovascular damage
     • Improve long-term outcomes 2

   • Immunosuppressive therapy based on severity of disease:

     • Mycophenolate mofetil (MMF)
     • Cyclophosphamide
     • Azathioprine
     • Calcineurin inhibitors (for class V nephritis)
     • Rituximab (for refractory disease) 2

3. Adjunctive therapies:

   • ACE inhibitors or angiotensin receptor blockers for proteinuria or hypertension
   • Statins for dyslipidemia
   • Anticoagulation in nephrotic syndrome with serum albumin <20 g/L 2

Liver Considerations

• Monitor liver function tests periodically
• Adjust medications based on liver function
• Reduce hydroxychloroquine dose in patients with liver disease 2

Special Considerations

Pregnancy

• Plan pregnancy when lupus is stable with inactive nephritis for at least 6 months
• GFR should preferably be >50 ml/min
• Continue hydroxychloroquine during pregnancy
• Consider acetylsalicylic acid to reduce pre-eclampsia risk 2

End-Stage Renal Disease

• All methods of renal replacement therapy can be used
• Increased risk of infections in peritoneal dialysis patients on immunosuppressants
• Increased risk of vascular access thrombosis in patients with antiphospholipid antibodies
• Transplantation should be performed when lupus activity has been absent or low for 3-6 months 2

Common Pitfalls to Avoid

1. Failing to regularly monitor patients with lupus for kidney involvement, even when asymptomatic
2. Reducing treatment intensity in anticipation of pregnancy
3. Stopping hydroxychloroquine unnecessarily (benefits usually outweigh risks)
4. Focusing only on glomerular changes while ignoring tubulointerstitial inflammation
5. Not addressing modifiable risk factors for CKD progression (hypertension, obesity, smoking)
6. Overlooking antiphospholipid antibodies which increase thrombotic risk

Remember that early detection and aggressive management of lupus nephritis are essential to prevent progression to end-stage kidney disease and improve long-term outcomes.